A number of model systems have been used to extend our understanding of amine metabolism, storage, and transport, and of the mechanism of action of tricyclic antidepressants. Systems studied include liposomes, mitochondria, eukaryotic cells, microvessels, nerve microsacs, and platelets. In addition to their effects on amine uptake, tricyclic antidepressants alter many aspects of energy metabolism in both mammalian mitochondria and eukaryotic cells of fungi and protozoa. Vesicular amine storage may mediated by the relative impermeability of the vesicle membrane to stored amines, and psycho-active substances known to cause amine release may act in part by increasing the membrane permeability. Both vesicular storage and amine uptake across the plasma membrane may be influenced by membrane lipid fluidity, and the action of some uptake inhibitors appears to be modulated by similar parameters.